Mechanisms of mechanical force-induced Rho family activation and actin cytoskeletal reorganization

2014 Fiscal Year Final Research Report

• Project/Area Number: 24370051
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Tohoku University
• Principal Investigator: MIZUNO Kensaku 東北大学, 生命科学研究科, 教授 (70128396)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 細胞・組織 / 細胞骨格 / Rho / メカニカルストレス / アクチン

Outline of Final Research Achievements

Rho family GTPases are crucial for mechanical force-induced actin cytoskeletal reorganization; however, the mechanism underlying force-induced activation of Rho family GTPases is unknown. A screen of short-hairpin RNAs targeting 63 Rho-guanine nucleotide exchange factors (Rho-GEFs) revealed that at least 11 Rho-GEFs are involved in cyclic-stretch-induced reorientation of vascular endothelial cells. Among 11 Rho-GEFs, Solo is involved in cell-cell-adhesion- and cadherin-mediated mechanical force-induced RhoA activation and reorientation of endothelial cells. We also identified at least 5 Rho-GEFs that are involved in extracellular matrix (ECM) stiffness-induced transformation of MCF-10A human breast epithelial cells cultured in 3D ECM conditions. Among them, Farp1 binds to integrins and plays a critical role in cell adhesion, proliferation, and morphogenesis.

Free Research Field

分子細胞生物学